Evaluation of Pre-Treatment Serum Levels of IL-7 and GM-CSF in Colorectal Cancer Patients

Survival of Colorectal cancer (CRC) patients is con siderably stage-dependent; therefore, early diagnos is is a pivotal factor in decreasing mortality and morbidit y associated with this cancer. GM-CSF and IL-7 are reported to increase in different cancers and we aimed to in vestigate the pre-treatment serum levels of GM-CSF and IL-7 in Iranian patients with colorectal cancer. 127 pat ients (68 males and 59 females) entered this study before receiving chemotherapy or radiotherapy. A control g r up of 50 healthy age/sex matched individuals (27 males and 23 females) were included in the study. The ser um levels of GM-CSF and IL-7 were measured using commercial enzyme linked immunosorbent assays. A significantly higher level of GM-CSF was found i n the sera of patients with colorectal cancer compared to healthy age/sex matched controls (P=0.013). Howeve r, th re was no significant difference between the levels of IL-7 in sera of patients and controls. We observed a significant elevation in the level of GM-CSF in poo rly differentiated tumors (P=0.024). Also a signifi cant correlation between lymphatic invasion and the leve l of GM-CSF in sera of CRC patients was detected (P =0.01). We found an increase of the level of IL-7 in four p atients presenting moderate stages of tumor concomi tant with a decrease of the level of GM-CSF. It can be conclu ded that the increase of the level of GM-CSF is acc ompanied by CRC progression in Iranian patients. Potential t herapeutic effect of IL-7 in this disease, however, needs further investigations.

nnually one million new cases of colorectal cancer (CRC) are diagnosed and half a million death occurs due to this cancer (1). It represents the third and second most common cancer in men and women respectively, (10% and 9.4% of all cancers, respectively) but its mortality is less in women than in men. The survival rate of CRC is significantly different in early stages versus A Submmited 16 Oct 2013; Accepted 15 Dec 2013 late stages (1). In fact, staging is the most important factor in evaluating the prognosis of colorectal cancer (2); therefore, early diagnosis and treatment can reduce mortality and morbidity of this cancer (1).
The immune system plays a dual role in the defence and development of many tumors.
Interestingly, tumor cells may exploit or produce effectors of the immune system for their own advantage. Colony Stimulating Factors (CSFs) are among the cytokines that are produced by cancer cells as well as the immune system in the course of tumorigenesis (3). Cytokines can also modulate several processes involved in tumor progression and metastasis, for example angiogenesis and the production of metalloproteinases (4).

Granulocyte Macrophage-Colony Stimulating
Factor (GM-CSF) is a cytokine that acts as a growth factor for white blood cells, and stimulates bone marrow to produce granulocytes and macrophages (5). GM-CSF is highly efficient in inducing specific immune responses resulting in tumor destruction (6). On the other hand, the production of GM-CSF correlates with the increase of recurrence rates in head and neck squamous cell carcinoma, possibly due to an inhibition of immune responsiveness (7). GM-CSF exerts an important role in regulation of intestinal immune and inflammatory responses (8). The establishment of normal colon epithelium is under the tight regulation of GM-CSF by controlling apoptosis and proliferation of these cells; therefore, GM-CSF deregulation is suggested to be a part of colon carcinogenesis. Moreover, GM-CSF can decrease apoptosis in colon cancer (9) and has a role in growth and cancer spreading (10 (12). IL-7 is a glycoprotein that is normally secreted

Patients
This study was approved by the Ethics

Samples
Four ml blood was collected from peripheral veins of patients on the day before surgery.

ELISA assays
The plasma level of GM-CSF was measured by a commercial enzyme linked immunosorbent assay (ELISA) (eBiosciences, Austria) according to the manufacturer's instructions. The sensitivity of this assay was 0.6 pg/ml and the range of detection was between 7.8-500 pg/ml. The serum level of IL-7 was measured using a commercial ELISA assay (Abcam, UK) according to the manufacturer's instructions. The sensitivity of this assay was less than 3 pg/ml and the range of detection was between 6.25-200 pg/ml.

Statistical analysis
Student's t-test was used for the analysis of age and gender distribution between the case and the control groups. One-way ANOVA or t-test was used for the comparisons between the two groups using SPSS software (11.5, Chicago, Illinois).
When the data points were less than 30 in categories, the normality of data was checked and parametric or non parametric (Kruskal-Wallis and Mann-Whitney) analyses were performed. Statistically significant differences were defined as comparisons resulting in p<0.05.

Results
A significantly higher level of GM-CSF    Accordingly, the level of GM-CSF was much higher in sera of patients with lymphatic invasion compared to those without lymphatic invasion (Table 4). No difference was observed in the level of IL-7 between the two groups of CRC patients.
[ Downloaded from ijmcmed.org on 2022-03-02 ] We also compared the level of the two cytokines between CRC patients presenting low stages (Stages 1 and 2), medium stages (Stages 3a and 3b) and high stages (stages 3c and 4) tumors.
We pg/ml and 30 ng/ml did not appear to affect the